Treatment Options for Thrombocytopenia in Cancer Patients

Abstract: Thrombocytopenia can limit administration of chemotherapy, which can adversely affect cancer patient outcomes. Management options ranging from innovations in medical management to invasive options are reviewed in this paper. While surgical management of splenectomy is addressed, the discussion focuses on contrasting techniques in splenic artery embolization highlighting implementation of total splenic artery embolization over partial splenic embolization. The former is an outpatient procedure that is safe and effective and should be considered in the management of chemotherapy-induced thrombocytopenia.

Key words: total splenic artery embolization, partial splenic artery embolization, thrombocytopenia, hypersplenism, cancer

______________________________________________

Thrombocytopenia in cancer patients can preclude administration of chemotherapy, limit frequency and intensity of chemotherapy. The mechanism of thrombocytopenia in cancer patients can be multifactorial. Decreased production of platelets secondary to chemotherapy and/or radiation therapy-induced myelotoxicity, are well established causes. Additionally, increased consumption of platelets secondary to chemotherapy-induced hypersplenism and hepatic damage may be contributors.¹ In solid tumors, chemotherapy delays and/or dose reductions are frequently recommended when platelets fall below 75,000 cells/mL. Platelet transfusions are often necessary to reduce bleeding complications once platelet counts reach 10,000 cells/mL to 20,000 cells/ mL.² Chemotherapy dose delays or dose reductions can negatively impact outcomes in patients with cancer.³

MEDICAL THERAPY FOR THROMBOCYTOPENIA

Frequent platelet count monitoring, chemotherapy dose reduction, and chemotherapy dose delay are routine for cancer patients receiving chemotherapy. Platelet transfusions are generally reserved for thrombocytopenia of 20,000 cells/mL or less in the absence of active bleeding or to higher platelet counts in the presence of bleeding.^2,4 Transfusion-related risks and high costs are frequent concerns.⁴ Several growth factors have been studied in the management of thrombocytopenia including oprelvekin (rIL-11;Neumega), the only FDA-approved agent for the prevention of chemotherapy-induced thrombocytopenia. However, the modest effect of oprelvekin on chemotherapy-induced thrombocytopenia and its high toxicity profile limit its clinical use.³

INVASIVE ALTERNATIVES

Invasive approaches aiming to reduce the sequestration of the platelets by the spleen have been explored in the management of chemotherapy-induced thrombocytopenia. Splenectomy is a rarely utilized alternative for management of thrombocytopenia due to high incidence of significant morbidities and complications, especially in immunocompromised patients. In the postoperative period, major complications include portal vein thrombosis and pancreatic leak leading to pseudocyst formation and severe sepsis.⁵

Other invasive options include partial radiofrequency ablation of the spleen, which has been studied in a group of 19 patients with thalassemia with good success.¹³

Splenic artery embolization provides an excellent alternative for management of a variety of causes of thrombocytopenia.Evaluation by a multidisciplinary team comprising medical oncologists,interventional radiologists, and hepatologists is required to determine a patient’s eligibility.

Once a patient is deemed eligible, the following are recommended:

1. Pretreatment laboratory studies including baseline complete blood count, liver function tests, renal function tests, and coagulation profile should be obtained.
2. Administration of vaccines for capsulated bacteria such as 23-valent pneumococcal polysaccharide vaccine (PPV-23), H influenza type B conjugate vaccine, and meningococcal vaccine should be considered prior to the procedure. The vaccination should be given at least 21 days prior to the procedure, allowing adequate time to mount effective immune response. Prophylactic antibiotics can also be considered prior to the procedure, for example ciprofloxacin, zosyn, clindamycin, and metronidazole.
3. Cross-sectional contrast enhanced imaging such as computed tomography or magnetic resonance imaging of the abdomen should be performed prior to the procedure in order to establish a baseline, which will be helpful in assessing splenic volume and rate of splenic infarction on postembolization follow-up. The imaging also aids in evaluating tortuosity, course, and diameter of the splenic artery.

Splenic artery embolization can be performed in two different manners, partial or total (proximal). Both options are discussed below in detail including advantages, disadvantages, and challenges.

PARTIAL SPLENIC ARTERY EMBOLIZATION

Partial splenic artery embolization (PSAE), which entails embolization of a portion of the splenic parenchyma utilizing embolic agents like gelfoam and polyvinyl alcohol particles has been demonstrated to be a safer alternative in compared to splenectomy and is considered the first-line therapy for thrombcytopenia secondary to hypersplenism.^5-8

Postembolization syndrome (PES),characterized by fever, nausea, vomiting, and abdominal pain is very common after PSAE, which necessitates admission to the hospital for most patients.The mean hospital stay after PSAE has been reported between 3-7 days.^1,5-9 PES is usually managed with analgesics and anti-inflammatory agents. Other complications reported with PSE include abscess,septicemia,splenic rupture, pancreatitis, and portal vein thrombosis.

TOTAL SPLENIC ARTERY EMBOLIZATION

Total splenic artery embolization (TSAE) is achieved by embolization of the proximal/main splenic artery using metal coils (Figure 1) or vascular plugs.¹⁰ The procedure is performed via right common femoral artery access and a sheath is placed using the standard Seldinger technique.The celiac artery is catheterized using a cobra head catheter where the splenic artery is subselected.An angiogram is performed to identify collateral circulation to the spleen and the pancreatic branches, including dorsal and greater pancreatic arteries.Afterwards, coil embolization of the proximal main splenic artery is performed distal to the origin pancreatic branches.The coils are oversized by 2 mm to 3 mm compared to the diameter of the vessel to prevent distal migration. Detachable coils are preferred whenever available. Anatomic variants may be encountered, including supply from the pancreatic magna artery to the spleen.In such instance,the pancreatic magna artery may be embolized distal to origin of the pancreatic feeders.

TSAE is a minimally invasive treatment modality that has traditionally been used in the treatment of a variety of conditions like splenic trauma, splenic artery aneurysm, and gastric variceal bleeding due to splenic thrombosis. More recently, TSAE has emerged as an option in the treatment of thrombocytopenia induced by hypersplenism and hepatic failure secondary to cirrhosis or chemotherapy.^6,11,12

COMPARISON OF TSAE AND PSAE

TSAE has shown to be a safer alternative in comparison to PSAE with better long-term results in hypersplenism related to cirrhosis. Platelet counts improve significantly after both the procedures and the improvement in the count usually peaks at 2 weeks after the procedure.⁶ A randomized trial comparing TSAE and PSAE demonstrated that both white blood cell counts and platelet counts are substantially higher following TSAE in comparison to PSAE, and that TSAE ensures a sustained and long-term increase in these hematologic parameters,with a slower increase in the residual splenic volume.⁶ TSAE has a lower incidence of postembolization syndrome in comparison to PSAE and can be safely performed on an outpatient basis or short hospital stay.^6,11,12

LONG-TERM FOLLOW-UP AFTER PSAE AND TSAE

Follow-up laboratory studies should be performed at 1 week, 1 month, 3 months, and 6 months followed by annually whenever possible. Follow-up imaging with computed tomography or magnetic resonance imaging is recommended to evaluate residual splenic volume or assess the extent of splenic infarction (Figure 2).The change in volume may not be seen initially and may become apparent after 3 months to 6 months.

SUMMARY

Medical therapies have been utilized to treat thrombocytopenia with limited success. Splenectomy is an invasive option with a high complication rate. Splenic artery embolization is a safe and effective option to alleviate thrombocytopenia induced by chemotherapy allowing resumption of therapy.PSAE has been a proven alternative for management of thrombocytopenia, but it is commonly associated with PES and long hospital stay. In contrast,TSAE is a relatively new and safer alternative that can be performed on an outpatient basis; it should be considered as an option in management of thrombocytopenia in cancer patients.6,11,12

REFERENCES

1. Kauffman CR, Mahvash A, Kopetz S,Wolff RA, Ensor J, Wallace MJ. Partial splenic embolization for cancer pa- tients with thrombocytopenia requiring systemic chemo- therapy. Cancer. 2008;112(10):2283-2288.
2. Schiffer CA, Anderson KC, Bennett CL, et al. Platelet transfusion for patients with cancer: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol. 2001;19(5):1519-1538.
3. Lyman GH. Impact of chemotherapy dose intensity on cancer patient outcomes. J Natl Compr Canc Netw. 2009;7:99-108.
4. Liou SY, Stephens J, Carpiuc KT, Feng W, Botteman MF, Hay JW. Economic burden of haematologi- cal adverse effects in cancer patients. Clin Drug Investig. 2007;27(6):381-396.
5. Sibulesky L, Nguyen JH, Paz-Fumagalli R,Taner CB, Dickson RC.Treatment modalities for hypersplenism in liver transplant recipients with recurrent hepatitis C. World J Gastroenterol. 2009;15(40):5010-5013.
6. He XH, Gu JJ, Li WT, et al. Comparison of total splenic artery embolization and partial splenic embolization for hypersplenism. World J Gastroenterol. 2012;18(24):3138- 3144.
7. Madoff DC, Denys A,Wallace MJ, et al. Splenic arterial interventions: anatomy, indications, technical con- siderations, and potential complications. Radiographics. 2005;25:S191-S211.
8. N’Kontchou G,Seror O,BourcierV,et al.Partial splenic embolization in patients with cirrhosis: efficacy, tolerance and long-term outcome in 32 patients. Eur J Gastroenterol Hepatol. 2005;17(2):179-184.
9. Gonsalves CF, Mitchell EP, Brown DB. Management of hypersplenism by partial splenic embolization with ethylene vinyl alcohol copolymer. Am J Roentgenol. 2010;195(5):1241-1244.
10. Widlus DM, Moeslein FM, Richard HM 3rd. Evaluation of the Amplatzer vascular plug for proximal splenic artery embolization. J Vasc Interv Radiol. 2008;19(5):652-656.
11. Bhatia S,Venkat S, Kably I,Yrizarry J, Froud T, Naray- anan G. Abstract No. 260: Splenic artery embolization for thrombocytopenia in chemotherapy recipients. J Vasc Intervent Radiol. 2013;24:S115.
12. He XH, Li WT, Peng WJ, Li GD,Wang SP, Xu LC.Total embolization of the main splenic artery as a supplemental treatment modality for hypersplenism. World J Gastroenterol. 2011;17(24):2953-2957.
13. Hashemieh M,Akhlaghpoor S,Azarkeivan A,Azizahari A, Shirkavand A, Sheibani K. Partial radiofrequency ab- lation of the spleen in thalassemia. Diagn Interv Radiol. 2012;18(4):397-402.

Editor’s note: This article underwent peer review by one or more members of the Interventional Oncology 360 editorial board.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no disclosures related to the content of this manuscript.

Suggested citation: Bhatia S, Venkat S, Rocha-Lima CM, Gonzalez E, Jun E, Narayanan G. Treatment options for thrombocytopenia in cancer patients. Intervent Oncol 360. 2013;1(4):E34-E38.